Transgenic Mouse Many in the biomedical sciences strongly believe that the progress of cancer research, and the position of the UCSD Cancer Center in the biomedical community during the next decade, will depend upon the ability to use the mouse as an experimental model to investigate both basic and clinically relevant questions in cancer research. The creation of new pre-clinical models of cancer in mice by genetic manipulation is specifically cited by the NCI as one of four extraordinary opportunities they wish to exploit. Transgenic mice carrying new or novel genes are created by microinjection of DMA into the pronuclei of fertilized eggs and "knock-out" mice lacking specific genes of interest are created by homologous recombination in embryonic stem cells followed by injection into blastocysts to create chimeric mice for breeding to homozygosity. The high degree of conservation of most sequences in genomes of humans and mice makes the idea of using mouse genetic manipulation technology to create models of human cancer pathogenesis extremely attractive. These approaches are remarkably powerful in cancer research particularly in the analysis of oncogenes, metastasis, cell-cycle control, tumor suppressor genes, and in the crafting of cancer model systems for developing new treatment regimens, and methods for drug testing and tumor imaging. The mission of this Shared Resource is to provide the highly technical aspects of manipulation of genes in embryos and embryonic stem cells as a service to our Center members, allowing them to create the genetically manipulated mouse models they need. This is an outstanding example of how specialized techniques, highly trained dedicated personnel, and expensive equipment can be accessed by researchers who could not reasonably expect to develop or obtain them on an individual basis. The availability of this Resource enables our researchers to conduct versatile, cutting-edge research with a battery of sophisticated genetic techniques.